This series of 3 double-blind, placebo-controlled (active placebo = diphenhydramine - 12.5 mg) studies examined the efficacy of medication plus individual counseling (Rounsaville's adaptation of interpersonal psychotherapy) for 12 weeks as outpatient treatment of drug abuse. Outcome was assessed by drug use (both urine toxicology and self-report), drug craving, mood, and psychosocial functioning (Addiction Severity Index). All subjects were followed up 3, 6, 12 months after active treatment. In the first study, 53 cocaine abusers (ages 21-60) were randomly assigned to receive either fluoxetine-20 mg (n=ll), 40 mg (14), 60 mg (12), or placebo (16) daily. All patients also received counseling twice weekly. There were no significant outcome differences among groups, whether analyzed in terms of medication dose or achieved plasma level (> vs < 100 ng/ml). At follow-up, all groups showed some improvement, with no group differences. In the second study, 45 PCP abusers were randomly assigned to receive either fluoxetine-20 mg daily or placebo, plus counseling twice weekly. In the third study, 46 cocaine abusers were randomly assigned to receive either desipramine-300 mg daily or placebo, plus counseling once weekly. Data from both studies are being analyzed.